Obesity is a complex chronic disease and a major driver of non-communicable diseases, including cardiovascular disease, type 2 diabetes, and several cancers ².  Obesity impacts populations across all countries and globally there are approximately 2.1 billion adults who are overweight or have obesity.  It is forecast that this will substantially rise to around 3.2 billion by 2050 – accounting for almost 60% of the adult population ³.

In their report, two main WHO conditional recommendations are:

• • GLP-1 therapies may be used for long term obesity treatment in adults (excluding pregnant women).
  • Alongside GLP‑1 therapies, structured behavioural interventions—such as healthy eating and increased physical activity—may be offered.

The WHO stresses that obesity cannot be addressed effectively by medications alone.  Their conditional recommendations are part of a strategy that includes regular physical activity, healthy diets, and support from healthcare professionals.  Therefore, three strategic pillars are identified to help combat obesity, in conjunction with GLP-1 therapeutics, namely:

1. Strengthen population level policies to create healthier environments.
2. Protecting high risk individuals with targeted screening and early interventions.
3. Ensuring equitable access to lifelong, person centred care.

The WHO guidance also highlights major challenges including high costs, limited supply, and disparities in global access.  Even with rapid scale up in production, fewer than 10% of people who could benefit from GLP-1 therapies are expected to have access by 2030.

Countries are being urged to establish fair and affordable routes so those with the greatest medical need are prioritised.  The guideance urges global stakeholders to explore strategies such as pooled procurement, tiered pricing, and voluntary licensing to expand availability.

Throughout 2026, the WHO aims to collaborate with key stakeholders to develop a fair, transparent and prioritised framework so those with the greatest need receive treatment first.

The therapeutic approach to obesity and type 2 diabetes mellitus (T2DM) is evolving in a similar way to how clinicians use antibiotics: targeting several pathways that often produce stronger and more durable effects than acting on a single pathway.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) laid the foundation, but the complexity of fat mass regulation quickly revealed the limits of one hormonal signal ¹.  This has led to multi-hormonal agents that act simultaneously on glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon, amylin, and/or peptide YY (PYY), better replicating the physiological and coordinated post-prandial response.

By engaging these pathways, the new therapies achieve broader and more synergistic metabolic improvements, marking a shift from single target drugs to integrated hormone-based treatment ¹.

GLP-1–Based Therapies

GLP-1 is secreted by intestinal endocrine cells after nutrient ingestion.  It enhances glucose-dependent insulin secretion, slows gastric emptying, reduces appetite, and promotes weight loss ^1–5.  Central nervous system GLP-1 signalling within the hypothalamus and brainstem is central to regulating fat mass ⁶.

Beyond glycaemia, GLP-1 exerts anti-inflammatory, endothelial, and lipid-modulating effects ¹.  Long-acting GLP-1RAs on their own such as semaglutide achieve substantial weight loss and glycaemic improvement, aided by gradual dose escalation strategies that improve tolerability ¹.

Oral semaglutide represents a significant advancement, using SNAC (sodium N-(8-[2-hydroxybenzoyl] amino) caprylate) to overcome gastrointestinal degradation and enable systemic absorption, despite low bioavailability (~1%) and strict fasting administration requirements ⁷.

Further innovations include small-molecule oral GLP-1RAs, such as orforglipron, which activate the GLP-1 receptor (GLP-1R) without peptide structures and offer simpler administration but without the same weight loss range ^1,8-9.

GIP-Related Therapies

GIP is also released by different endocrine cells in the small intestine.  It stimulates insulin secretion during normoglycemia and influences lipid storage, though its metabolic effects are highly context-dependent ¹.

Importantly, both GIP receptor (GIPR) agonism and GIPR antagonism have been shown to reduce body weight; an unexpected therapeutic paradox ¹.  Central GIPR signalling suppresses appetite in rodents, while peripheral GIP actions vary with insulin sensitivity ^1,10.  In humans, exogenous GIP shows limited appetite loss (anorectic) effects, suggesting species-specific physiological differences ¹¹.

GLP-1/GIP Dual Agonists

Dual agonism of the GLP-1R and GIPR aims to capitalise on complementary hormonal effects.  Tirzepatide is the first approved dual GLP-1/GIP agonist and achieves greater weight loss and glycaemic improvement than semaglutide alone, suggesting synergistic incretin modulation ¹².  Additional co-agonists, including SCO-094, VK2735, CT-388, and DR10627, are under development to refine receptor balance and broaden metabolic benefits ¹.

Unimolecular GLP-1RAs/GIPR Antagonists

In contrast to co-agonists, unimolecular agents combining GLP-1R activation with GIPR blockade exploit evidence that GIPR antagonism enhances weight loss by disrupting adipogenic GIP signalling and amplifying GLP-1 driven satiety pathways ¹.

Maridebart cafraglutide (formerly AMG-133) exemplifies this approach by merging GLP-1 agonism with a monoclonal GIPR-blocking antibody.  Monthly dosing produces meaningful body weight reductions (12–16%) and improves glycaemia in people with obesity and T2DM ^1,13.  Pre-clinical work with the GIPR antagonist AT-7687 shows similar synergy when paired with GLP-1RAs ¹.

Oxyntomodulin Physiology and Oxyntomodulin-Based Therapies

Oxyntomodulin (OXM) is also secreted by the endocrine cells in the intestine but does not have a dedicated receptor.  Instead OXM binds to both the glucagon and GLP-1R ¹⁴.  Glucagon as a standalone peptide is secreted by pancreatic alpha-cells.  It increases hepatic glycogenolysis and gluconeogenesis during fasting but also regulates satiety, enhances hepatic β-oxidation, reduces liver fat, and increases energy expenditure ^1,15.

OXM mimics many of these same effects when it binds the glucagon receptors ¹⁴.  These metabolic properties support OXM use within multi-agonist therapies, without the risk of pure glucagon’s inherent hyperglycaemic potential.

OXM analogues (GLP-1/Glucagon Co-agonists)

Co-activation of GLP-1R and glucagon receptors leverages the anorectic and insulinotropic actions of GLP-1 with glucagon-driven increases in energy expenditure.  Survodutide and mazdutide are leading examples.  Survodutide has demonstrated up to 13–15% weight loss, alongside significant improvement in metabolic dysfunction–associated steatohepatitis (MASH) ^1,16-17.  Mazdutide produces dose-dependent weight reduction and glycaemic improvement with good tolerability ¹⁸.

Triple GIP/GLP-1/Glucagon Co-agonists

Retatrutide is a triple agonist that simultaneously activates GLP-1Rs, GIPRs, and glucagon receptors.  This design aims to maximise appetite suppression and thermogenesis.  In phase 2 trials, retatrutide achieved approximately 17–18% weight loss in individuals with obesity without T2DM, surpassing most available pharmacotherapies ^1,19.

Amylin Physiology and Amylin-Based Therapies 

Amylin is co-secreted with insulin and slows gastric emptying, suppresses glucagon, and increases satiety through pathways distinct from other anorectic hormones ^1,20.  Long-acting analogues such as cagrilintide produce clinically significant weight loss ²¹.

Amylin/GLP-1 Dual Agents

CagriSema, a fixed combination of semaglutide and cagrilintide that integrates GLP-1–mediated appetite suppression with amylin driven satiety and gastric emptying effects.  Recent trials show approximately 23% weight loss, exceeding either monotherapy or approaching metabolic surgery efficacy ^1,21.

Peptide YY Physiology and Related Medicines

Peptide YY (PYY) is co-secreted with GLP-1 by endocrine cells in the intestine and converted to its active form PYY 3-36, which acts via Y2 receptors to inhibit neuropeptide Y (NPY) neurons and promote satiety ^1,22.   After bariatric surgery, postprandial PYY, GLP-1, and OXM rises sharply and contributes to improved adipocyte mass regulation.  Early PYY analogues show reduced food intake and modest weight loss in short-term studies ^1,22.

Table 1.  Comparison Table of Novel GLP-1–Based Medications

Conclusion

Together, these advances mark a decisive shift in obesity and T2DM therapeutics from a single pathway modulation toward integrated, multimodal hormone-based interventions.

GLP-1 remains the backbone, but layering complementary signals from GIP, glucagon, amylin, and PYY allows for unprecedented degrees of weight reduction and metabolic restoration, as summarised for comparison in Table 1.

As uni-, dual-, and triple-molecular agents continue to refine receptor balance, the field is rapidly approaching the efficacy once achievable only through metabolic surgery.

The emerging challenge is no longer whether we can produce profound metabolic benefits, but rather how to optimise durability, individualise receptor targeting, and translate these complex pharmacologic innovations into long term clinical decision making.

This therapeutic evolution represents not merely incremental drug development, but a redefinition of how we conceptualise and treat the chronic diseases of obesity and type 2 diabetes.

In recent years, pharmacological interventions have emerged as important adjuncts to traditional weight loss approaches.  These obesity medications, such as Glucagon Like Peptide-1 Receptor Agonists (GLP-1 RAs), have gained significant attention for their promising efficacy in achieving weight loss.  Currently, there are several GLP-1 RA medications delivered by injection, which are sold under various brand names, though availability and licensing vary significantly by country (Table 1).

Table 1. Examples of Global Usage of GLP-1 RAs for Weight Management

GLP-1 RAs are prescription-only pharmaceutical drugs and not dietary supplements.  They must be prescribed and monitored by a qualified healthcare professional.  Furthermore, it must be emphasised that holistic treatment strategies including lifestyle and dietary changes should be included alongside GLP-1 RAs medications.

Unsurprisingly, where data is available, GLP-1 RA usage continues to accelerate, particularly with the forthcoming release of an oral form, which will likely make medications lower cost and more widely accessible.  Additionally, usage is likely to further increase given upcoming expiring patents from 2026 onwards ^9,10, enabling the provision of more widespread, lower cost formulations.

It is estimated that in the US, over 90 million adults are eligible for GLP-1 RAs, with approximately 26 million adults eligible in the UK.  In the US, individuals with overweight or obesity using GLP-1 RAs has increased from 21,000 in 2019 to 174,000 in 2023, which is a 700% increase in usage ¹¹.  In Australia in 2023, there were approximately 2.5 million prescriptions for Semaglutide alone under the Pharmaceutical Benefits Scheme, which is nearly double the previous year’s total prescription ¹².  However, globally, real usage is likely higher given the difficulties accurately quantifying usage due to the burgeoning private market.

While North America held the largest market share for GLP-1 RA medications in 2024, with Europe following, Asia-Pacific is expected to exhibit the fastest growth market due to rising diabetes and obesity rates ¹³.  Although the Middle East and Africa market is currently smaller, it is also projected to grow significantly in the coming years ¹⁴.  GLP-1 RAs face a mix of regulatory hurdles across Latin America, shaped by fragmented healthcare systems, evolving drug policies, and rising demand.  Yet, the Latin American GLP-1 RA market is expected to grow by a third in the next five years ¹⁵.

Understanding the Biological Effects of GLP-1 RAs

GLP-1 RAs, also known as GLP1-analogs or incretin mimetics, are a class of obesity medications originally developed for the management of type 2 diabetes.  They mimic the action of endogenous GLP-1, a hormone naturally released by cells in the small intestine in response to food intake and exert effects ¹⁶ (Figure 1) in a dose-dependent manner ¹⁷.Figure 1. Physiological Effects of GLP-1 RAs.

Primarily, GLP-1 RAs help regulate blood glucose levels by stimulating insulin secretion from pancreatic beta cells, whilst decreasing the production of glucagon, a hormone that increases blood glucose.  Additionally, GLP-1 RAs modulate the hypothalamus (the region in the brain that controls appetite) to regulate hunger, slow gastric emptying, and regulate gut hormones such as leptin (a hormone that helps regulate body weight on a long-term basis).  Consequently, this prolongs the feeling of fullness (satiety), reduces appetite, and reduces overall calorie intake – subsequently leading to negative energy balance and weight loss ¹⁸.

Efficacy of GLP-1 RAs in Weight Loss
GLP-1 RAs have consistently demonstrated effectiveness for weight loss in clinical trials among individuals with obesity compared with placebo treatments ^17,18.  Those using GLP-1 RAs achieve clinically meaningful weight loss of between 5 to 24% of their initial body weight, depending on dosing regime and type of drug administered. Furthermore, reductions in the incidence of cardiovascular events have also been evidenced ¹⁹.

GLP-1 RA Side Effects and Adherence
Despite the promising efficacy of GLP-1 RAs for weight loss, dropout rates in clinical trials and adherence concerns in real-world settings are notable.  Real‐world studies demonstrate high discontinuation rates of GLP‐1RAs by up to 75% within the first year of use, predominantly driven by side effects ^20-22.  Common side effects include gastrointestinal symptoms such as nausea, vomiting, diarrhoea, and constipation.  Other side effects may include headaches, dizziness, fatigue, and injection site reactions.  Rare, but potentially serious, side effects of GLP-1 RAs may include pancreatitis and gallbladder disease, as highlighted by The UK Medicines and Healthcare Products Regulatory Agency in 2024 ²³.

Whilst GLP-1 RA usage is effective at driving weight loss, the magnitude varies depending on factors such as the type of GLP-1 RA used, treatment duration, and the individual.  Weight regain following discontinuation of these medications is common (Figure 2), with up to two-thirds of weight loss being regained within the first year ²⁴.  This is likely driven by the lack of education surrounding lifestyle and behaviour change strategies adopted by GLP-1 RA users, which would encourage continued healthy lifestyle habits following medication cessation.

Figure 2. Weight Regain After GLP-1 RA Discontinuation ²⁴.  Reproduced from Wilding et al. ²⁴, © [2022], published by Wiley, under CC-BY license.

Dietary Intakes of GLP-1 RA Users – what is scientific evidence telling us?

Most of the general population fall short of achieving a healthy, balanced diet.  For example, many populations are not meeting the recommendations for fibre intake including those in Argentina, Canada, China, Lithuania, South Africa, the UK, and US.  Further, from national and international dietary survey data across the globe, sugar, saturated fat and sodium intakes remain above recommended levels.  Consequently, achieving a nutritionally adequate, balanced diet may be particularly challenging for GLP-1 RA users, who consume a reduced proportion of their usual daily intake, unless careful attention is given to food choices.

A narrative review of 10 primary studies that assessed energy intakes in GLP-1 RA users revealed that total calorie intake was reduced by 16 to 39% in a single meal ²⁵.  However, the most common measurement of food intake was a standardized test meal followed by an ad libitum lunch, dinner, or snack.  This method has inherent limitations and data should be treated with caution.  Only one study included in the review used a validated 24-h dietary recall method.  Interestingly, when data is studied in more detail, reported calorie intake remains adequate and in line with recommendations for GLP-1 RA users.  For example, reported daily energy intake of GLP1-RA users is approximately 1750 to 2180 kcal per day.  So perhaps meeting recommended nutrient intakes remains achievable.

Beyond changes in calorie intake, only eight studies, to date, have evaluated changes in macronutrient intake in GLP-1 RA users.  Unfortunately, data is inconsistent among these studies, likely due to the different methodologies used between studies, making it difficult to provide firm conclusions.  Perhaps more concerning is that 11 to 50% of total weight loss in GLP-1 RA users is attributed to loss of lean body mass, which may detrimentally include loss of skeletal muscle ²⁶, potentially negatively impacting metabolism, strength and long-term health.  Thus, protein intake, alongside physical activity, remains a priority to minimise muscle loss for GLP-1 users.

GLP-1 RA Recommendations

In studies evaluating combined GLP-1 RA with nutrition and lifestyle interventions, individuals receiving both GLP-1 RAs and structured dietary guidance achieved greater weight loss, better adherence, and were more likely to sustain weight loss after discontinuing GLP-1 RAs compared to those receiving the medication alone ²⁷.

Although limited information currently exists regarding specific dietary reference intakes for individuals using obesity medications, a recent Joint Advisory highlights specific areas of nutritional concern for GLP-1 users (Figure 3) ²⁷.  For example, protein intakes of up to 1.5 g/kg/day have been suggested for this population ²⁸.  Yet, in practice, these protein levels are likely difficult to achieve in a population of GLP-1 RA users who have 1) a higher body mass and 2) a reduced energy intake.  Future protein intake recommendations should be based on lean mass-adjusted body weight rather than total body weight, as protein requirements are largely determined by lean tissue rather than fat mass.

Figure 3. Key elements of nutritional priorities to support GLP-1 therapy users for obesity ²⁷.  Reproduced from Mozaffarian et al. ²⁷, © [2025], published by Wiley, under CC-BY license.

For Healthcare Professionals (HCPs)
Tailored approaches to GLP-1 RA treatment plans are needed to ensure sustainable weight loss strategies, improve patient adherence, and support healthier dietary intakes.  Previous research has recommended nutritional priorities to support GLP-1 RA users (Figure 3).  These recommendations can enable healthcare professionals (HCPs) to better guide GLP-1 RA users toward lasting health improvements.  For example, HCPs should discuss the importance of balanced nutritional intake with all patients prescribed GLP-1 RAs, alongside monitoring signs of malnutrition, micronutrient status, and changes in body composition.

Given the limitations in accurately quantifying body composition using more accessible body compositional measurement tools (e.g., bioelectrical impedance), physical function should also be monitored.  Further, to promote sustained weight management, GLP-1 RA users should be educated on healthy diets and physical activity recommendations, and support should be available to encourage long term behaviour change.

For Researchers
There is a clear need for future research to examine changes in dietary intake and nutrient status following use of obesity medications using robust study designs with validated, accurate methods for measuring daily habitual intakes.  Given that, to our knowledge, only two studies have estimated micronutrient intake in GLP-1 RA users ^29,30, more research is needed to both quantify changes in micronutrient intake and status in this population.

Further, whilst some anecdotal and qualitative data suggests that GLP-1 RAs effectively reduced food-related thoughts (‘food noise’) and support healthier eating behaviours, more objective data is needed.  Mechanistically, more research is needed to investigate whether GLP-1 RAs influence nutrient absorption and subsequent bioavailability, incorporating measurements of the gut microbiota diversity and composition, and nutrient biomarkers.

Such research will help develop nutritional guidance to best support GLP-1 RA users.  Information available on dietary reference intakes for individuals using obesity medications is minimal ²⁸, and currently not well-evidenced.

An Industry Perspective on Innovating for GLP-1 Users

The surge in GLP-1 RA usage for weight loss is set to increase demand for products with a wide range of attributes.  Portion size, protein and fibre content, and digestive health are the key areas for consideration.

There are a few strategic approaches that are currently gaining momentum across the food, beverage and supplement industries ³¹ (Figure 4).  One strategy is to position existing products as complementary solutions for GLP-1 RA users.  Focusing on gut health aids that might alleviate gastrointestinal side effects and nutritional supplements that help offset deficiencies linked to reduced food intake.  Another approach is to launch products that are nutrient-dense and portion-controlled for both GLP-1 RA users and individuals tapering off the medication who continue to sustain weight loss whilst preserving muscle mass.

Figure 4. GLP-1 RA Strategic Approaches for Industry ³¹.

In Summary

GLP-1 RAs represent a valuable therapeutic option to achieve weight loss and improve overall health when prescribed safely and appropriately alongside dietary and behavioural support and increased physical activity.

By balancing the potential benefits and risks of treatment using evidence-based strategies, HCPs are well placed to help optimise the use of GLP-1 RAs in the management of obesity and overweight.  This will ultimately support individuals in achieving their weight loss goals while minimising adverse effects.

Research is still required to evidence nutritional intake in GLP-1 RA users, and to subsequently inform dietary recommendations that are specific for this population.  Nutritious products must be accessible to GLP-1 users to achieve healthy eating habits that provide essential nutrients, vitamins, and minerals.

Authors’ Note: The authors recognize the fast-evolving nature of GLP-1 research and trends and will endeavour to ensure the article remains current with emerging GLP-1 RA data.

On October 14th, 2025, the KHNI hosted an expert scientific webinar; “Adapting Appetites: Scientific and Industry Perspectives on the rise of GLP-1 Medications”.  The expert panel explored the latest science behind Glucagon Like Peptide-1s (GLP-1s), consumer behaviours across regions, the unique nutritional needs of users and what this means for future innovation in food and beverages.

Latest Scientific Insights on GLP-1s

Professor Catherine Godson, Professor of Molecular Medicine, University College Dublin (UCD) and Director of the UCD Diabetes Complications Research Centre, began her session discussing the evolution of GLP-1s which were initially indicated for people with type 2 diabetes.  Given that GLP-1s result in weight loss, the next approach was to explore if they had a positive effect on people with obesity.  Professor Godson highlighted GLP-1 established indications as well as other indications that are under investigation.  Interestingly, Catherine pointed out that the incretin hormone GLP-1 not only acts on the cells in the pancreas but also in other areas of the body such as the brain.  Professor Godson concluded her session addressing the efficacy, safety, and tolerability of GLP-1s.

Regional Trends in GLP-1 User Behaviour

Elizabeth Horvath, VP of Marketing for Kerry North America, took us through findings from GLP-1 consumer surveys conducted by Kerry in the US (quantitative survey) and the UK (qualitative survey).  The quantitative survey looked at GLP-1 users’ purchase drivers and preferences whereas the qualitative survey explored GLP-1 user habits throughout the entire day to understand their daily activities.  Elizabeth highlighted there were five very specific GLP-1 consumers, each on their own health journeys, and that their attitudes and behaviours shift at every stage of the GLP-1 journey.  Interestingly, the North America study showed that two-thirds of GLP-1 users are actively seeking functional benefits from their food, beverages, and supplements.  Among their top priorities are support for cognitive function, digestive wellness, and immune health.  Elizabeth shared insights into how GLP-1 users’ buying habits are changing, especially in foodservice and retail.

Nutrition Essentials for GLP-1 Users

Next, Angie Jefferson focused on the nutritional needs of GLP-1 users.  Initially, Angie introduced the different GLP-1 medications on the market.  Currently, there are few good quality trials exploring the impact of GLP-1 medication on consumer eating habits, dietary intakes, and/or their impact on nutritional status.  Angie pointed out that a much higher proportion of weight loss in GLP-1 users is attributed to loss of lean body mass; however, GLP-1 use combined with resistance exercise can help preserve or increase muscle mass.  Angie provided insights into the nutritional status and emerging needs of GLP-1 users.  She also noted that discontinuing GLP-1 treatment often leads to weight regain, with a tendency toward increased body fat percentage.  Angie wrapped up by stressing an urgent gap exists in dietary and lifestyle guidance for GLP-1 users.

Innovation Opportunities in Food & Drink for GLP-1 Users

Dr Alexandra Boelrijk, Kerry VP R&D Proactive Health and Food Protection, looked at opportunities and challenges when considering products for GLP-1 users.  Alexandra pointed out that the food and beverage companies early to market with products that meet demands of various GLP-1 users have opportunities to defend share as well as drive growth.  Dr Boelrijk highlighted that forward-thinking brands are addressing the needs of GLP-1 users by reformulating products with higher protein, fibre, and micronutrients and/or by developing functional foods that support gut health, satiety, and metabolic support.  Alexandra concluded by discussing the new formats of products that have launched in the market for GLP-1 users.

During the Q&A session, moderator Mark Faherty posed thoughtful questions to the speakers.  He concluded the webinar by expressing gratitude to Angie, Alexandra, Catherine, and Elizabeth for sharing their time and expertise.